3-Hydroxyadamantaneglyoxylic acid (1) is an important intermediate for the synthesis of pharmacologically active dipeptidyl peptidase inhibitors, which inhibit cleavage of a peptide GLP-1 (7-36), responsible for stimulating insulin secretion and promotion of satiety and slowing of gastric emptying. PCT publication WO 2004/052850 discloses the following method of preparation of 3-hydroxyadamantaneglyoxylic acid (1) (Scheme 1):

The method comprises a ZnCl2-catalyzed coupling of 1-bromoadamantane (3) with tris(trimethylsiloxy)-ethylene in the environmentally difficult solvent dichloromethane to give the α-hydroxy acid derivative (4). Compound (4) was then esterified with a methanol/acetyl chloride solution to provide the α-hydroxy ester derivative (5). Swern oxidation of (5) at the technologically troublesome low temperature (keeping the internal temperature below −60° C.) with the assistance of hazardous oxalyl chloride yielded the glyoxylic ester (6). The ester (6) was then oxidized into the corresponding 3-hydroxy compound (7). Finally, hydrolysis of (7) with sodium hydroxide yielded the target molecule (1).
As can be seen, processes for the preparation of 3-hydroxyadamantaneglyoxylic acid have so far been laborious, hazardous and unpractical.